Nalazite se na CroRIS probnoj okolini. Ovdje evidentirani podaci neće biti pohranjeni u Informacijskom sustavu znanosti RH. Ako je ovo greška, CroRIS produkcijskoj okolini moguće je pristupi putem poveznice www.croris.hr
izvor podataka: crosbi !

Human dipeptidyl-peptidases (h.DPP III), sampling the substrate binding site - computational analysis (CROSBI ID 574900)

Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija

Tomić, Antonija ; Tomić, Sanja Human dipeptidyl-peptidases (h.DPP III), sampling the substrate binding site - computational analysis // Book of Abstracts of the "Fourth Humboldt Conference on Computational Chemistry" / Petrova, P. Galina ; Vayssilov, N. Georgie (ur.). Sofija, 2010. str. 63.-63

Podaci o odgovornosti

Tomić, Antonija ; Tomić, Sanja

engleski

Human dipeptidyl-peptidases (h.DPP III), sampling the substrate binding site - computational analysis

Human dipeptidyl-peptidases plays a significant role in the protein catabolism, pain regulation and defense against oxidative stress.1, 2, 3 It hydrolyzes dipeptides from the N-terminal of its substrates. We performed series of molecular dynamics (MD) simulations for the complexes between the enzyme, wild type (WT) and its H568N and W300L mutants, and both synthetic and natural ligands, Arg-Arg-2-naphthylamide (RRNA), Tyr-Phe-hydroxamate and endomorphine-1 (EM-1), respectively. We accomplished 30 ns of MD simulations for the complexes between WT and the H568N mutated h.DPP III with synthetic ligands. For the complexes with EM-1 we performed 4 ns and for the free W300L mutant of h.DPP III and its complex with RRNA 3 ns of MD simulations. Systems simulated 30 ns show octahedral coordination of the central zinc ion. In the other systems the zinc coordination sphere is still not stable mainly due to fluctuations of the active site Glu508 and His450. MD simulations revealed the enzyme subsites S1, S2, S1' and S2' as well as the substrate N-terminus recognition site pointing out that both, synthetic and natural ligands bind into the h.DPPIII active site in a similar manner. Ligand binding induced reorganization of the binding site and its partial closure. Further MD simulations are required to: a) thoroughly investigate the EM-1 binding into the active site, and b) to elucidate effects of the Trp to Leu mutation on the complex stability. Also, using the QM/MM methodology we plan to shed some light on the hydrolysis that takes place in the DPP III active site. [1] Ellis S, Nuenke JM (1967) J Biol Chem 242, 4623 [2] Abramić M, Zubanović M, Vitale Lj (1988) Biol Chem Hoppe-Seyler 369, 29 [3] Chen JM, Barrett AJ (2004) In: Barret AJ, Rawlings ND, Woessner JF (eds) Handbook of Proteolytic Enzymes, vol 1. Elsevier, Academic Press, London, pp 809-812

Human dipeptidyl-peptidases; molecular dynamics simulations

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

Podaci o prilogu

63.-63..

2010.

objavljeno

Podaci o matičnoj publikaciji

Book of Abstracts of the "Fourth Humboldt Conference on Computational Chemistry"

Petrova, P. Galina ; Vayssilov, N. Georgie

Sofija:

Podaci o skupu

Fourth Humboldt Conference on Computational Chemistry

poster

12.07.2010-15.07.2010

Varna, Bugarska

Povezanost rada

Kemija